This invention relates to a medical diagnostic method and, more particularly, to an in vitro diagnostic method for determining the presence of nerve growth factor receptor bearing tumors.
The presence of specific soluble proteins in human serum or urine has been useful in the detection and diagnosis of a variety of tumor and disease states and in measuring the efficacy of medico-surgical management of these conditions. Among these soluble factors are Bence Jones proteins in patients with multiple myeloma, carcinoembryonic antigen (CEA), and epidermal growth factor in patients with small cell and epidermoid carcinoma of the lung, medullary thyroid carcinoma, as well as carcinomas of the stomach and esophagus. Recently, another such protein, interleukin 2 receptor (IL-2R), has gained considerable attention as a potential marker for various autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis, gout, bacterial endocarditis, type I insulin dependent diabetes, and active chronic autoimmune hepatitis, as well as a potential marker for T- and B-cell leukemia.
The implication of nerve growth factor (NGF) or its receptor (NGFR) in neoplasia in the central and peripheral nervous system has been considered for a number of years. See, e.g., R. Levi-Montalcini, Science 237, 1154-1166(1987), for a review of the history of NGF research. As a result, determination of the presence of NGFR in human cells and tissue has been proposed as a means of diagnosis for certain tumors. Thus, Fabricant et al., Proc. Natl. Acad. Sci. U.S.A. 74(2), 565-569 (1977), describe the presence of NGFR on human melanoma cells (A875) in culture. It was reported that purified mouse NGF (2.5S,.beta.-subunit preparation) when radiolabeled with .sup.125 I was found to bind readily with the A875 melanoma cells.
More recently, Ross et al., Proc. Natl. Acad. Sci. U.S.A. 81, 6681-6685 (1984), characterized the NGFR in neural crest tumors using monoclonal antibodies. The monoclonal antibodies were prepared, for example, by using human melanoma cell line WM245 cells as the immunogen in mice for obtaining hybridoma cells to produce monoclonal antibody 20.4 (IgG). It was shown that the NGFR is expressed on melanoma cells in much greater quantities than on normal melanocytes.
In European Patent Application No. 202,005, published Nov. 20, 1986, a diagnostic method for the detection of neural crest tumors is disclosed which consists of contacting human cells with antibody that is specific for NGFR having an average molecular weight of about 75,000 daltons.
The foregoing methods for determining NGFR levels involve histochemical identification which necessitate the inconvenient invasive procedure of making a biopsy of the test tissue.